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Hans-Henrik Parving

Publications and source records attributed to Hans-Henrik Parving.

At least 19 recordsLinked to original sources
PubMed2007

An IGF-I gene polymorphism modifies the risk of developing persistent microalbuminuria in type 1 diabetes.

OBJECTIVE: Derangements of the GH-IGF-I axis have been associated with microalbuminuria (MA) in type 1 diabetes. The aim of this study was to investigate whether an IGF-I gene promoter polymorphism influenced the development of persistent MA in type 1 diabetes. DESIGN: A prospective follow-up study of a cohort of 277 patients with newly diagnosed type 1 diabetes consecutively enrolled between September 1979 and August 1984. METHODS: Urinary albumin excretion rate over 24 h was measured in each patient at least once a year. Persistent MA was defined as a urinary albumin excretion rate between 30 and 300 mg/24 h. RESULTS: During a median follow-up of 18.0 years (range 1.0-21.5), 79 of 277 patients developed persistent MA. IGF-I gene genotype was available for 216 subjects; in 73% of the subjects, the wild-type genotype of this IGF-I gene polymorphism was present, while 27% had the variant type. At baseline, there were no differences in IGF-I levels and HbA(1c) values between subjects with the wild type and subjects with variant type. By Kaplan-Meier analysis, subjects with the variant type of this polymorphism had during follow-up a higher risk of development of MA compared subjects with the wild type (P = 0.03). CONCLUSIONS: Subjects with the variant type of an IGF-I gene polymorphism had a significantly increased risk of developing MA. This risk was not mediated through changes in circulating IGF-I levels. Our study suggests that in type 1 diabetes, this IGF-I gene polymorphism is a risk factor of MA.

Adolescent↗
PubMed2006

Subclinical coronary and aortic atherosclerosis detected by magnetic resonance imaging in type 1 diabetes with and without diabetic nephropathy.

BACKGROUND: Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic nephropathy using cardiovascular magnetic resonance imaging. METHODS AND RESULTS: In a cross-sectional study, 136 subjects with long-standing type 1 diabetes without symptoms or history of cardiovascular disease, including 63 patients (46%) with nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden, expressed as right coronary artery mean wall thickness (1.7+/-0.3 versus 1.3+/-0.2 mm; P<0.001) and maximum right coronary artery wall thickness (2.2+/-0.5 versus 1.6+/-0.3 mm; P<0.001), was greater in subjects with nephropathy. The prevalence of thoracic (3% versus 0%; P=0.28) and abdominal aortic plaque (22% versus 16%; P=0.7) was similar in both groups. Subjects with and without abdominal aortic plaques had similar coronary plaque burden. CONCLUSIONS: In asymptomatic type 1 diabetes, cardiovascular magnetic resonance imaging reveals greater coronary plaque burden in subjects with nephropathy compared with those with normoalbuminuria.

Adult↗
PubMed2006

Mannose-binding lectin and mortality in type 2 diabetes.

BACKGROUND: Inflammation and complement activation initiated by mannose-binding lectin (MBL) may be implicated in the pathogenesis of diabetic vascular complications. We evaluated the relationship between serum MBL and mortality and development of albuminuria in type 2 diabetes. METHODS: Levels of MBL and C-reactive protein (CRP) were measured at baseline in 326 patients with type 2 diabetes who attended the Steno Diabetes Center, Gentofte, Denmark, for control. Urinary albumin excretion was determined annually, and the vital status of all patients was traced after more than 15 years of follow-up. RESULTS: During follow-up, 169 patients died. The risk of dying was significantly higher among patients with MBL levels greater than or equal to 1000 microg/L than among patients with levels less than 1000 microg/L (hazard ratio, 1.5; 95% confidence interval, 1.1-2.1; P = .005). After adjustment for known confounders, MBL remained a significant risk factor for death from any cause. It added to the predictive power of CRP, and mortality was significantly higher among patients with both high MBL (> or =1000 microg/L) and high CRP (above the median, 3.6 mg/L) levels than among patients with both low MBL and low CRP levels (hazard ratio, 2.7; 95% confidence interval, 1.7-4.3; P<.001). Normoalbuminuric patients with both high MBL and high CRP levels at baseline had a significantly increased risk of developing microalbuminuria or macroalbuminuria compared with patients with both low MBL and low CRP levels (hazard ratio, 2.6; 95% confidence interval, 1.5-4.4; P<.001). CONCLUSION: In patients with type 2 diabetes, measurements of MBL alone or in combination with CRP can provide prognostic information on mortality and the development of albuminuria.

Albuminuria↗
PubMed2006

Microalbuminuria as an early marker for cardiovascular disease.

Excretion of albumin in the urine is highly variable, ranging from nondetectable quantities to milligrams of albumin and even grams of albumin. Microalbuminuria is defined as low levels of urinary albumin excretion of 30 to 300 mg/d. Microalbuminuria is highly prevalent; in hypertensive and diabetic populations, its prevalence varies from 10 to 40%. It is interesting that microalbuminuria also is found frequently in seemingly healthy individuals (5 to 7%). The variable excretion of albumin in the urine is related to the risk for the individual to develop cardiovascular (CV) disease: Absence or very low levels of albuminuria is associated with low CV risk, whereas the CV risk increases markedly with increasing amount of albumin in the urine (even within the now considered normal range). The predictive power of urinary albumin levels for CV risk is independent of other CV risk factors and not only is present in individual with diabetes and/or hypertension but also in healthy individuals. Treatments that lower albuminuria are associated with CV protection, as demonstrated in randomized, controlled trials of patients with diabetes as well as in patients with hypertension. There is preliminary evidence that albuminuria lowering is CV protective in healthy individuals with an elevated albumin excretion rate. Differences between individuals in their level of albumin excretion are already observed at a very early age (just after birth). In fact, the interindividual variability seems to be relatively constant in the first 5 decades of life, indicating that microalbuminuria is not necessarily a consequence of vascular damage at later age. Higher levels of urinary albumin seem to reflect the ordinary interindividual variability in (renal and systemic) endothelial function. Experimental data show that between strains and even within strains, rats at young age show a remarkable difference in individual endothelial function, and this is strongly related to the susceptibility of that rat to organ damage. In conclusion, albuminuria seems to be a sensitive marker very early in life for the susceptibility of an individual to CV disease. It therefore may be an ideal target for early primary prevention using CV-protective therapy regimens.

Albuminuria↗
PubMed2006

PROactive study.

Explore the source record for details and available documents.

Blood Pressure↗
PubMed2006

An extension of the Early Treatment Diabetic Retinopathy Study (ETDRS) system for grading of diabetic macular edema in the Astemizole Retinopathy Trial.

PURPOSE: To compare the effects of astemizole, an antihistamine, versus placebo on the 1-year course of diabetic macular edema (DME) and to illustrate use of a modified ETDRS system for grading areas of retinal thickening and hard exudates that may be useful in clinical trials of treatments for this disorder. METHODS: Between June 1994 and September 1997, at 2 clinics, 63 patients who had, in at least one eye (the study eye), DME that had not previously been treated with macular photocoagulation, and for which photocoagulation was not currently recommended by the investigator, were enrolled and randomly assigned to astemizole or placebo. Fifty-four of the 63 patients (86%, 26 in Clinic 1 and 28 in Clinic 2) completed 1 year of followup and had adequate 7-field stereoscopic film-based color fundus photographs of the study eye at the baseline and 1-year visits. DME was > 0.33 disc diameters (DD) from the center of the macula in 48% of study eyes and involved the center in 13%. Photographs were graded using the ETDRS protocol modified to allow estimates of areas of retinal thickening (RT) and hard exudate (HE) to be made on continuous scales in disc area (DA) units. Principal outcome measures were mean change in the square root of RT area (the average diameter of the area in DD), mean change in area of HE, and change in the degree to which RT involved or threatened the center of the macula. RESULTS: At baseline, RT area in the 54 study eyes ranged from 0.09 to 4.0 DA (median 1.1). At the 1-year visit the square root of RT area (RTdd) had decreased by > or= 0.3 DD in 10 eyes, increased by >or = 0.3 DD in 19 and was about the same in 25. Mean change at 1 year was +0.09 DD (SD 0.57) for astemizole versus +0.19 DD (SD 0.48) for placebo, for a difference of -0.10 DD (95% CI -0.38, +0.19; p = 0.51). Adjustments for baseline and time-dependent risk factors did not change this result appreciably, although there was a trend towards a difference in favor of astemizole in the subgroup of patients with more severe retinopathy. Other morphologic outcomes paralleled change in RTdd. Change in RTdd did vary by clinic: -0.03 DD in Clinic 2, versus + 0.32 DD in Clinic 1, for a difference of -0.35 DD (95% CI -0.62, -0.07; p = 0.014). Clinic 1 is a tertiary retinal referral center in Pennsylvania and Clinic 2 a retinal clinic closely affiliated with a large diabetes clinic in Copenhagen. The unexpected clinic difference in outcome provided an opportunity for further analyses using the modified ETDRS system. In comparison to Clinic 1, Clinic 2 patients were more often male, were younger at diagnosis of diabetes, and had less severe retinopathy and better visual acuity, but these differences did not appear to explain the trend for lesser increase in RTdd. CONCLUSION: No effect of astemizole was found, but the confidence interval for the principal outcome, mean change in RTdd, included both a modest beneficial effect and a small harmful effect. This outcome measure did demonstrate a small difference in outcome by clinic, which could not be explained by baseline characteristics but may reflect differences in access to and/or continuity of care or other unmeasured differences associated with different referral patterns. Although optical coherence tomography may supplant photography as a measure of central RT, photographic assessments of change in RT and HE areas analyzed with the methods described herein may be useful outcomes in trials assessing treatment of early stages of DME. Application of these methods to other data sets is needed to confirm this conclusion.

Adult↗
PubMed2006

A French cost-consequence analysis of the renoprotective benefits of irbesartan in patients with type 2 diabetes and hypertension.

OBJECTIVES: We performed a cost-consequence analysis in a French setting of the renoprotective benefit of irbesartan in hypertensive type 2 diabetes patients over a 25-year period. RESEARCH DESIGN AND METHODS: A previously published Markov model simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease and death. Three treatment strategies with analogous blood pressure control were compared: (A) control--conventionally medicated antihypertensive therapy (excluding angiotensin converting enzyme inhibitors, other angiotensin-2-receptor antagonists and dihydropyridine calcium channel blockers) initiated at microalbuminuria; (B) early irbesartan--(300 mg daily added to control, initiated with microalbuminuria) and (C) late irbesartan--(300 mg daily, initiated with overt nephropathy). Probabilities came from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial and other sources. Clinical and economic outcomes were projected over 25 years. Annual discount rates were 3%. RESULTS: Compared to control, early use of irbesartan added (mean +/- standard deviation) 1.51 +/- 0.08 undiscounted life years (discounted: 0.94 +/- 0.05 years), while late irbesartan added 0.07 +/- 0.01 (0.04 +/- 0.01) years/patient. Early irbesartan added 1.03 +/- 0.06 discounted quality-adjusted life years (QALYs), while late irbesartan added 0.06 +/- 0.01 QALYs. Early and late irbesartan treatments were projected to save 22,314 +/- 1273 euro and 6619 +/- 820 euro/patient, respectively versus control. Sensitivity analysis showed that even over short time horizons both irbesartan treatments were superior to the control group. CONCLUSIONS: In France, early irbesartan treatment improved quality and length of life and reduced costs in hypertensive patients with type 2 diabetes and microalbuminuria. Late irbesartan therapy is beneficial, but earlier irbesartan leads to better outcomes.

Albuminuria↗
PubMed2006

Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients.

OBJECTIVE: The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed in patients with diabetes. In this study, we examined whether plasma OPG is associated with the glycaemic and vascular status of patients with type 1 diabetes. METHODS: Two gender-, age- and duration-comparable groups of type 1 diabetic patients either with (n = 199) or without (n = 192) signs of diabetic nephropathy were studied. Plasma OPG was determined by an ELISA. RESULTS: The plasma OPG concentration was significantly higher in patients with nephropathy than those without (3.11 (2.49-3.99) vs 2.57 (2.19-3.21) (median (interquartiles), ng/ml), P < 0.001). Plasma OPG correlated with haemoglobin A1c (HbA1c), systolic blood pressure and age in both groups and, in addition, with kidney function in the nephropathic group. These correlations remained significant in multivariate models. In addition, we found that plasma OPG concentrations were increased among patients with cardiovascular diseases (CVD), both in the normoalbuminuric and the nephropathic groups. The differences between nephropathic and normoalbuminuric, as well as subgroups with and without CVD, could largely be ascribed to changes in HbA1c, age, systolic blood pressure and creatinine. CONCLUSION: OPG is associated with glycaemic control and CVD in patients with type 1 diabetes, compatible with the hypothesis that OPG is associated with the development of diabetic vascular complications.

Adult↗
PubMed2006

Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: strongest evidence for association with a variant in the promoter region of the adiponectin gene.

Linkage studies have mapped loci for diabetic nephropathy and associated phenotypes on chromosome 3q. We studied 14 plausible candidate genes in the linkage region because of their potential role in vascular complications. In a large-scale study of patients from Denmark, Finland, and France who have type 1 diabetes, 1,057 case and 1,127 control subjects, as well as 532 trios, were investigated for association with diabetic nephropathy. We analyzed 69 haplotype-tagging single nucleotide polymorphisms and nonsynonymous variants that were identified by sequencing. Polymorphisms in three genes, glucose transporter 2 (SLC2A2), kininogen (KNG1), and adiponectin (ADIPOQ), showed nominal association with diabetic nephropathy in single-point analysis. The T-allele of SLC2A2_16459CT was associated with a decreased risk of diabetic nephropathy (odds ratio 0.79 [95% CI 0.66-0.96], P = 0.016), whereas the T-allele of KNG_7965CT and the A-allele of ADIPOQ_prom2GA were associated with increased risk of nephropathy (1.17 [1.03-1.32], P = 0.016; 1.46 [1.11-1.93], P = 0.006, respectively). Analyses of the transmission disequilibrium test showed similar trends only for ADIPOQ_prom2GA with the overtransmission of the A-allele to patients with diabetic nephropathy (1.52 [0.86-2.66], P = NS) and of the G-allele to patients without diabetic nephropathy (0.50 [0.27-0.92], P = 0.026). The overall significance for this variant (nominal P = 0.011) suggests that ADIPOQ might be involved in the development of diabetic nephropathy.

Chromosome Mapping↗
PubMed2006

Irbesartan treatment reduces biomarkers of inflammatory activity in patients with type 2 diabetes and microalbuminuria: an IRMA 2 substudy.

The impact of irbesartan treatment on biomarkers of low-grade inflammation, endothelial dysfunction, growth factors, and advanced glycation end products (AGEs) during the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study was evaluated. IRMA 2 was a 2-year multicenter, randomized, double-blind trial in patients comparing irbesartan (150 or 300 mg once daily) versus placebo. The primary end point was onset of overt nephropathy. A subgroup (n = 269, 68%) was analyzed for biomarkers at baseline and after 1 and 2 years. High-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, fibrinogen, adhesion molecules, transforming growth factor-beta, and AGE peptides were assessed. Irbesartan treatment yielded significant changes in hs-CRP (based on generalized estimating equation regression coefficient) with a 5.4% decrease per year versus a 10% increase per year in the placebo group (P < 0.001). Fibrinogen decreased 0.059 g/l per year from baseline versus placebo's 0.059 g/l increase per year (P = 0.027). IL-6 showed a 1.8% increase per year compared with placebo's 6.5% increase per year (P = 0.005). Changes in IL-6 were associated with changes in albumin excretion (P = 0.04). There was no treatment effect on the other biomarkers. Irbesartan (300 mg once daily) reduces low-grade inflammation in this high-risk population, and this may reduce the risk of micro- and macrovascular disease.

Aged↗
PubMed2006

Cardiac autonomic neuropathy predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy.

OBJECTIVE: Cardiac autonomic neuropathy (CAN) has been associated with a poor prognosis in patients with diabetes. Because CAN is common in patients with diabetic nephropathy, we evaluated the predictive value of CAN in type 1 diabetic patients with and without diabetic nephropathy. RESEARCH DESIGN AND METHODS: In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy and a matched group of 191 patients with long-standing type 1 diabetes and normoalbuminuria were followed for 10.1 years (range 0.0-10.3 years). At baseline, CAN was assessed by heart rate variation (HRV) during deep breathing. HRV was evaluated as a predictor of the primary end point: cardiovascular morbidity and mortality. As secondary end points, all-cause mortality and the influence of HRV on progression of diabetic nephropathy (decline in glomerular filtration rate [GFR]) was evaluated. RESULTS: During the follow-up, 79 patients (40%) with nephropathy reached the combined primary end point vs. 19 patients (10%) with normoalbuminuria (log-rank test, P < 0.0001). The unadjusted hazard ratio (HR) for reaching the primary end point when having an abnormal HRV (< or =10 bpm) measured at baseline compared with a normal HRV was 7.7 (range 1.9-31.5; P = 0.004) in patients with nephropathy. Similarly in the normoalbuminuric patients, the unadjusted HR was 4.4 (1.4-13.6; P = 0.009). In patients with nephropathy, abnormal HRV was significantly associated with fatal and nonfatal cardiovascular disease after adjustment for cardiovascular risk factors. The adjusted HR for reaching the primary end point in a patient with nephropathy and an abnormal HRV was 6.4 (1.5-26.3, P = 0.010), as compared with a normal HRV. The unadjusted HR for dying when having an abnormal HRV compared with a normal HRV was 3.3 (95% CI 1.0-10.7; P = 0.043) in patients with diabetic nephropathy. After adjustment for confounding factors, the impact of HRV on all-cause mortality in patients with nephropathy was no longer significant (P = 0.293). There was no relationship between abnormal HRV and rate of decline in GFR. CONCLUSIONS: HRV is an independent risk factor for cardiovascular morbidity and mortality in type 1 diabetic patients with nephropathy.

Adult↗
PubMed2006

Urinary connective tissue growth factor excretion correlates with clinical markers of renal disease in a large population of type 1 diabetic patients with diabetic nephropathy.

OBJECTIVE: Levels of connective tissue growth factor (CTGF; CCN-2) in plasma are increased in various fibrotic disorders, including diabetic nephropathy. Recently, several articles have reported a strong increase of urinary CTGF excretion (U-CTGF) in patients with diabetic nephropathy. However, these studies addressed too small a number of patients to allow general conclusions to be drawn. Therefore, we evaluated U-CTGF in a large cross-sectional study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 318 type 1 diabetic patients and 29 normoglycemic control subjects. U-CTGF was measured by sandwich enzyme-linked immunosorbent assay. Groups were compared by Kruskal-Wallis and Mann-Whitney analysis. The relation between U-CTGF and markers of diabetic nephropathy was determined by regression analysis. RESULTS: U-CTGF in patients with diabetic nephropathy (n = 89, median 155 pmol/24 h [interquartile range 96-258]) was significantly higher than in microalbuminuric (n = 79, 100 [65-78]) and normoalbuminuric (n = 150, 85 [48-127]) patients and control subjects (n = 29, 100 [78-114]). U-CTGF correlated with urinary albumin excretion (UAE) (R = 0.31) and glomerular filtration rate (R = -0.38) in patients with diabetic nephropathy. A standardized increase in U-CTGF was associated with diabetic nephropathy (odds ratio 2.3 [95% CI 1.7-3.1]), which was comparable with the odds ratios for diabetic nephropathy of increased HbA(1c) (2.0 [1.5-2.7]), and blood pressure (2.0 [1.5-2.6]). CONCLUSIONS: This is the first large cross-sectional study addressing U-CTGF in human type 1 diabetes. The observed association of U-CTGF with UAE and glomerular filtration rate might reflect a role of CTGF as progression promoter in diabetic nephropathy.

Adult↗
PubMed2006

Monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy.

OBJECTIVE: The purpose of this study was to assess agreement between glomerular filtration rate (GFR) and the decline in GFR estimated with the Modification of Diet in Renal Disease (MDRD) Study Group equation or the Cockcroft-Gault formula and measured by the plasma clearance of 51Cr-EDTA. RESEARCH DESIGN AND METHODS: We followed a cohort of 156 microalbuminuric type 2 diabetic patients for 8 years with four measurements of GFR and another cohort of 227 type 2 diabetic patients with overt diabetic nephropathy for 6.5 (range 3-17) years with seven (3-22) measurements of GFR. RESULTS: For patients with microalbuminuria, mean +/- SD baseline GFR was 117 +/- 24 measured, 92 +/- 20 estimated (MDRD equation), or 103 +/- 24 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001); 95% limits of agreement were -66.1 to 20.3 (MDRD equation) and -58.7 to 30.7 (Cockcroft-Gault formula). The rate of decline in GFR was 4.1 +/- 4.2 measured, 2.9 +/- 2.8 estimated (MDRD equation), or 3.4 +/- 3.2 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). For patients with overt nephropathy, baseline GFR was 84 +/- 30 measured, 73 +/- 24 estimated (MDRD equation), or 81 +/- 28 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001) with 95% limits of agreement -47 to 25 (MDRD equation) and -39 to 33 (Cockcroft-Gault formula). The rate of decline in GFR was 5.2 +/- 4.1 measured, 4.2 +/- 3.8 estimated (MDRD equation), and 4.6 +/- 4.1 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). CONCLUSIONS: Particularly in microalbuminuric (hyperfiltering) patients, GFR is significantly underestimated with wide limits of agreement by the MDRD equation as well as by the Cockcroft-Gault formula. The rate of decline in GFR is also significantly underestimated with both equations. This makes GFR estimations based upon these equations unacceptable for monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy.

Albuminuria↗